O'Shaughnessy P J, Fleming L M, Jackson G, Hochgeschwender U, Reed P, Baker P J
Institute of Comparative Medicine, University of Glasgow Veterinary School, Glasgow, Scotland G61 1QH, United Kingdom. p.j.o'
Endocrinology. 2003 Aug;144(8):3279-84. doi: 10.1210/en.2003-0277.
Adult Leydig cell steroidogenesis is dependent on LH but fetal Leydig cells can function independently of gonadotropin stimulation. To identify factors that may be involved in regulation of fetal Leydig cells expressed sequence tag libraries from fetal and adult testes were compared, and fetal-specific genes identified. The ACTH receptor [melanocortin type 2 receptor (Mc2r)] was identified within this fetal-specific group. Subsequent real-time PCR studies confirmed that Mc2r was expressed in the fetal testis at 100-fold higher levels than in the adult testis. Incubation of fetal or neonatal testes with ACTH in vitro stimulated testosterone production more than 10-fold, although ACTH had no effect on testes from animals aged 20 d or older. The steroidogenic response of fetal and neonatal testes to a maximally stimulating dose of human chorionic gonadotropin was similar to the response shown to ACTH. The ED(50) for ACTH, measured in isolated fetal and neonatal testicular cells, was 5 x 10(-10) M and the lowest dose of ACTH eliciting a response was 2 x 10(-11) M. Circulating ACTH levels in fetal mice were around 8 x 10(-11) M. Neither alpha-MSH nor gamma-MSH had any effect on androgen production in vitro at any age. Fetal testosterone levels were normal in mice that lack circulating ACTH (proopiomelanocortin-null) indicating that ACTH is not essential for fetal Leydig cell function. Results show that both LH and ACTH can regulate testicular steroidogenesis during fetal development in the mouse and suggest that fetal Leydig cells, but not adult Leydig cells, are sensitive to ACTH stimulation.
成年睾丸间质细胞的类固醇生成依赖于促黄体生成素（LH），但胎儿睾丸间质细胞可独立于促性腺激素刺激发挥功能。为了确定可能参与胎儿睾丸间质细胞调节的因子，比较了胎儿和成年睾丸的表达序列标签文库，并鉴定出胎儿特异性基因。促肾上腺皮质激素（ACTH）受体[黑皮质素2型受体（Mc2r）]在这个胎儿特异性基因组中被鉴定出来。随后的实时定量聚合酶链反应（PCR）研究证实，Mc2r在胎儿睾丸中的表达水平比成年睾丸高100倍。体外将胎儿或新生儿睾丸与ACTH共同孵育可使睾酮生成增加10倍以上，不过ACTH对20日龄及以上动物的睾丸没有影响。胎儿和新生儿睾丸对最大刺激剂量的人绒毛膜促性腺激素的类固醇生成反应与对ACTH的反应相似。在分离的胎儿和新生儿睾丸细胞中测得的ACTH半数有效剂量（ED50）为5×10-10 M，引发反应的最低ACTH剂量为2×10-11 M。胎儿小鼠的循环ACTH水平约为8×10-11 M。α-促黑素细胞激素（α-MSH）和γ-促黑素细胞激素（γ-MSH）在任何年龄对体外雄激素生成均无影响。缺乏循环ACTH（阿黑皮素原基因缺失）的小鼠胎儿睾酮水平正常，这表明ACTH对胎儿睾丸间质细胞功能并非必不可少。结果表明，LH和ACTH在小鼠胎儿发育过程中均可调节睾丸类固醇生成，提示胎儿睾丸间质细胞而非成年睾丸间质细胞对ACTH刺激敏感。
